The primary purpose of this program project is to better define the cellular and molecular defects that contribute to cyst development in AD/ARPKD and in the long term to devise strategies for treatment. The purpose of Core B is twofold: first, to provide the program Investigators with the support and expertise for all studies requiring access to a comprehensive repository of human kidney tissue and cell lines, to make available viral gene delivery methods , to provide assistance with functional assays and to assist the Investigators with all aspects involving the use of mice. Second, in parallel to supporting the mechanistic studies proposed, Core B will be responsible for developing AAV based strategies for therapeutic gene delivery to the kidney in the future. Specifically: Aim 1 is designed to provide a service for the cloning of viral vectors, the production, purification and titration and quality control of recombinant viruses. A second part of this Aim will be to explore the feasibility of AAV mediated gene delivery to specific cell types of the kidney. Very little is known about the potential for AAV based vectors to treat kidney specific disease. This Core is uniquely qualified to tackle this problem in a comprehensive manner. Aim 2 is designed to expand and maintain a central repository of human kidney tissues and cell lines derived from normal fetal and adult proximal tubules, thick ascending limbs of Henle and collecting tubules as well as cystic epithelia from ADPKD and ARPKD kidneys. The Core will obtain and process kidney tissues, culture and characterize primary and conditionally immortalized cultures and make frozen stocks. In addition assistance will be provided for Investigators with tissue histology, immunostaining, in situ hybridization as well as functional adhesion, migration and tubulogenesis assays and microinjection into mouse embryonic kidney organ cultures. Aim 3. will create transgenic mouse lines to better elucidate the role of polycystin and sprouty genes implicated in the control of cystogenesis. Transgenic mice will be produced and screened for development of renal abnormalities, surgical procedures and microdissections of normal, transgenic and ARPKD model mice will be carried out. Core Investigators have developed and will provide a microinjection procedure to introduce foreign genes into fetal and newbom mouse kidneys which will allow evaluation of potential therapeutic maneuvers.